title: Drug exposure: inclusion of dispensed drugs before pregnancy may lead to underestimation of risk associations.
abstract: OBJECTIVE
  To assess the impact of exposure misclassification on risk associations when using prescription databases as the source for drug exposure in pregnancy by applying results from a validation analysis of exposure classification.
  
  
  METHODS
  Linkage of data on 27,656 participants in the Norwegian Mother and Child Cohort Study (MoBa) with the Norwegian Prescription Database (NorPD). Exposure to selective serotonin reuptake inhibitors (SSRIs) was defined by dispensed drugs during pregnancy including different time windows before pregnancy. The validity of NorPD data was estimated using self-reported use in MoBa as the reference standard. We applied the results from the validation analysis on data from a Nordic study on SSRI use in pregnancy and risk of persistent pulmonary hypertension in the newborn.
  
  
  RESULTS
  Sensitivity increased and specificity decreased when the time window in NorPD was expanded before pregnancy. Using the same time window as in the Nordic study (+90 days before pregnancy), for use in early pregnancy, the odds ratio (OR) corrected for misclassification was 2.6 compared with the OR of 1.6 in the Nordic study.
  
  
  CONCLUSIONS
  Expansion of the time window to include intervals before pregnancy can lead to lower specificity and underestimation of risk associations.
authors.affiliation: Department of Pharmacoepidemiology, Division of Epidemiology, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo, Norway. svetlana.skurtveit@fhi.no
authors.forename: Svetlana
authors.initials: S
authors.lastname: Skurtveit
authors.forename: Randi
authors.initials: R
authors.lastname: Selmer
authors.forename: Aage
authors.initials: A
authors.lastname: Tverdal
authors.forename: Kari
authors.initials: K
authors.lastname: Furu
authors.forename: Wenche
authors.initials: W
authors.lastname: Nystad
authors.forename: Marte
authors.initials: M
authors.lastname: Handal
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects*; D016208:Databases, Factual; D003863:Depression / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D009664:Norway; D016017:Odds Ratio; D010547:Persistent Fetal Circulation Syndrome / Q000139:chemically induced*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D055553:Prescription Drugs / Q000009:adverse effects*; D011446:Prospective Studies; D015203:Reproducibility of Results; D018570:Risk Assessment; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D055553:Prescription Drugs; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Misclassification; MoBa; Pregnancy; Prescription databases; SSRI exposure; Validity